Roux-en-Y Gastric Bypass Improves Metabolic Conditions in Association with Increased Serum Bile Acids Level and Hepatic Farnesoid X Receptor Expression in a T2DM Rat Model
机构：[1]Department of General Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China[2]Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China大德路总院检验科大德路总院检验科广东省中医院[3]Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China[4]Department of General Surgery, Central Hospital of Fengxian District, Southern Medical University, No.6600, Nan Feng Road, Shanghai 201499, China
Background Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the effects of RYGB on glucose homeostasis, lipid metabolism, and liver morphological adaption, as well as the changes in bile acids signaling and expression of its target regulatory factors involved in gluconeogenesis, lipogenesis, and fatty acid beta oxidation. Methods Twenty adult male T2DM rats induced by high-fat diet and a low dose of streptozotocin were randomly divided into sham and RYGB groups. The parameters of body weight, food intake, glucose tolerance, insulin sensitivity, serum lipid profiles, and bile acids level were assessed to evaluate metabolic changes. Liver sections were stained with hematoxylin-eosin (H&E) and oil red O to assess lipid accumulation. The mRNA and protein expression levels of farnesoid X receptor (FXR), small heterodimer partner (SHP), key regulatory factors of gluconeogenesis, lipogenesis, and fatty acid beta oxidation (phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-alpha (PPAR-alpha)) were determined through RT-PCR and Western blotting, respectively. Results RYGB induced significant improvements in glucose tolerance and insulin sensitivity, along with weight loss and decreased food intake. RYGB also decreased serum TG, FFAs, and increased bile acids levels. The lipid droplets in the liver were significantly decreased after RYGB. The RYGB group exhibited downregulated mRNA and protein expression levels of PEPCK, G6Pase, and SREBP-1c and upregulated expression of FXR, SHP, and PPAR-alpha in the liver. Conclusions RYGB ameliorates glucose and lipid metabolism accompanied by weight loss and calorie restriction. The liver exhibited a marked improvement in lipid accumulation after RYGB. The bile acids level, FXR, and its target transcriptional factor SHP expression were elevated. Meanwhile, our study demonstrated that the increased bile acids-FXR signaling, followed by the reduced hepatic gluconeogenesis, lipogenesis, and increased fatty acid beta oxidation may contribute to improved metabolic conditions after RYGB.
基金：
Science and
Technology Project of Guangzhou Health and Family Planning
Commission (Grant No. 20181A011027).
第一作者机构：[1]Department of General Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Yan Yong,Sha Yanhua,Huang Xianzhang,et al.Roux-en-Y Gastric Bypass Improves Metabolic Conditions in Association with Increased Serum Bile Acids Level and Hepatic Farnesoid X Receptor Expression in a T2DM Rat Model[J].OBESITY SURGERY.2019,29(9):2912-2922.doi:10.1007/s11695-019-03918-0.
APA：
Yan, Yong,Sha, Yanhua,Huang, Xianzhang,Yuan, Wei,Wu, Fan...&Zhang, Xueli.(2019).Roux-en-Y Gastric Bypass Improves Metabolic Conditions in Association with Increased Serum Bile Acids Level and Hepatic Farnesoid X Receptor Expression in a T2DM Rat Model.OBESITY SURGERY,29,(9)
MLA：
Yan, Yong,et al."Roux-en-Y Gastric Bypass Improves Metabolic Conditions in Association with Increased Serum Bile Acids Level and Hepatic Farnesoid X Receptor Expression in a T2DM Rat Model".OBESITY SURGERY 29..9(2019):2912-2922
